SUMMARY Human cytomegalovirus (HCMV) is the most frequent cause of congenital infection and a leading non-genetic cause of hearing loss and neurologic disabilities in children, yet no efficacious preventative vaccine is available. About 50% of infants exposed to HCMV in breast milk will become infected by 6 months of age providing a natural HCMV acquisition model with a unique opportunity to define antiviral immune responses that prevent transmission at the mucosal surface. Studies of T cell-mediated immunity in breast milk have been limited. In humans, little is known about the types of T cells and their function in breast milk and whether they play a role in the control and the transmission of pathogens to the infant. In addition, this information will allow us to begin to understand what effector T cell populations are desirable for effective vaccines and/or immunotherapies. This knowledge is especially pertinent in the context of HCMV transmission to the infant via breast milk because this is a unique in vivo model of natural HCMV acquisition in humans. Lastly, these studies will also add new information to the study of human mucosal immunology. !